This proposal deals with the relationship of three newly identified polypeptides, vasoactive intestinal peptide (VIP) and two vasoactive lung peptides, to a number of malignant tumors. Using a sensitive and specific radioimmunoassay (RIA), VIP has been shown to occur normally in the gastrointestinal and nervous systems, and in elevated concentrations in these tumors: pancreatic (islet-cell) adenomas, pheochromocytoma, neuroblastoma, medullary thyroid carcinoma, and bronchogenic carcinoma. The clinical syndrome in common among these tumors was that of watery diarrhea (pancreatic cholera), accompanied in some instances by hyperglycemia, hypercalcemia, hypokalemia and episodic flushing. One vasoactive lung peptide, extractable from normal lung, is related to VIP, cross-reacting with it in the RIA. The other vasoactive lung peptide is spasmogenic and does not cross-react with VIP. Determination of the prevalence of secretion of these peptides in the presence of malignant disease may provide useful clues to the early diagnosis, better management and, possibly also, the pathogenesis of these lesions.